This comprehensive analysis of effector pathways and regulatory mechanisms of immediate hypersensitivity and inflammation in the lung will focus on macrophage functions; mechanisms of immunologically-stimulated formation and release of chemical mediators and their biodegradation by isolated pulmonary cells; and alpha-globulin modulation of primary and amplifying reactions in the inflammatory responses of the lung. Investigations will involve the controls of both in vitro migration of alveolar macrophages and their in vivo clearance of particles from the lung. IgE-mediated induction of synthesis and release of chemical mediators from purified mast cells and other lung cells will provide a model for assessment of the regulation of each phase including the inactivation of the mediators. The effects of alpha-globulin inhibitors, especially alpha-1-antitrypsin, on proinflammatory enzymes derived from leukocytes and other pulmonary cells will be studied with a view both to the direct actions of the proteases and to the functions of mediators liberated by their cleavage of protein substrates.